title: MRI of coronary wall remodeling in a swine model of coronary injury using an elastin-binding contrast agent.
abstract: BACKGROUND
  The extracellular matrix (ECM) plays an important role in the pathogenesis of atherosclerosis and in-stent restenosis. Elastin is an essential component of the ECM. ECM degradation can lead to plaque destabilization, whereas enhanced synthesis typically leads to vessel wall remodeling resulting in arterial stenosis or in-stent restenosis after stent implantation. The objective of this study was to demonstrate the feasibility of MRI of vascular remodeling using a novel elastin-binding contrast agent (BMS-753951).
  
  
  RESULTS
  Coronary injury was induced in 6 pigs by endothelial denudation and stent placement. At day 28, delayed-enhancement MRI coronary vessel wall imaging was performed before and after injection of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA). Two days later, DE-MRI was repeated after administration of BMS-753951. Contrast-to-noise-ratio and areas of enhancement were determined. Delayed-enhancement MRI with BMS-753951 caused strong enhancement of the aortic, pulmonary artery, and injured coronary artery walls, whereas Gd-DTPA did not. Delayed-enhancement MRI of the stented coronary artery with BMS-753951 yielded a 3-fold higher contrast-to-noise-ratio when compared with the balloon-injured and control coronary artery (21±6 versus 7±3 versus 6±4; P<0.001). The area of enhancement correlated well with the area of remodeling obtained from histological data (R(2)=0.86, P<0.05).
  
  
  CONCLUSIONS
  We demonstrate the noninvasive detection and quantification of vascular remodeling in an animal model of coronary vessel wall injury using an elastin-specific MR contrast agent. This novel approach may be useful for the assessment of coronary vessel wall remodeling in patients with suspected coronary artery disease. Further studies in atherosclerotic animal models and degenerative ECM disease are now warranted.
authors.affiliation: Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, Germany. christian.von-bary@klinik.uni-regensburg.de
authors.forename: Christian
authors.initials: C
authors.lastname: von Bary
authors.forename: Marcus
authors.initials: M
authors.lastname: Makowski
authors.forename: Anne
authors.initials: A
authors.lastname: Preissel
authors.forename: Alexandra
authors.initials: A
authors.lastname: Keithahn
authors.forename: Alice
authors.initials: A
authors.lastname: Warley
authors.forename: Elmar
authors.initials: E
authors.lastname: Spuentrup
authors.forename: Arno
authors.initials: A
authors.lastname: Buecker
authors.forename: Joel
authors.initials: J
authors.lastname: Lazewatsky
authors.forename: Richard
authors.initials: R
authors.lastname: Cesati
authors.forename: David
authors.initials: D
authors.lastname: Onthank
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Schickl
authors.forename: Sylvia
authors.initials: S
authors.lastname: Schachoff
authors.forename: Jörg
authors.initials: J
authors.lastname: Hausleiter
authors.forename: Albert
authors.initials: A
authors.lastname: Schömig
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.forename: Simon
authors.initials: S
authors.lastname: Robinson
authors.forename: René
authors.initials: R
authors.lastname: Botnar
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation; D000818:Animals; D003287:Contrast Media / Q000378:metabolism; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D003331:Coronary Vessels / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism*; D005240:Feasibility Studies; D005260:Female; D019786:Gadolinium DTPA; D006335:Heart Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D011237:Predictive Value of Tests; D015607:Stents; D013552:Swine; D013997:Time Factors; D057772:Vascular System Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology*
chemical_list: D003287:Contrast Media; D004549:Elastin; D019786:Gadolinium DTPA